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Wilms tumor (WT) is the most common childhood kidney cancer worldwide and poses a cancer health disparity to black children of sub-Saharan African ancestry. Although overall survival from WT at 5 years exceeds 90% in developed countries, this pediatric cancer is alarmingly lethal in sub-Saharan Africa and specifically in Kenya (36% survival at 2 years). Although multiple barriers to adequate WT therapy contribute to this dismal outcome, we hypothesized that a uniquely aggressive and treatment-resistant biology compromises survival further. To explore the biologic composition of Kenyan WT (KWT), we completed a next generation sequencing analysis targeting 10 WT-associated genes and evaluated whole-genome copy number variation. The study cohort was comprised of 44 KWT patients and their specimens. Fourteen children are confirmed dead at 2 years and 11 remain lost to follow-up despite multiple tracing attempts. TP53 was mutated most commonly in 11 KWT specimens (25%), CTNNB1 in 10 (23%), MYCN in 8 (18%), AMER1 in 5 (11%), WT1 and TOP2A in 4 (9%), and IGF2 in 3 (7%). Loss of heterozygosity (LOH) at 17p, which covers TP53, was detected in 18% of specimens examined. Copy number gain at 1q, a poor prognostic indicator of WT biology in developed countries, was detected in 32% of KWT analyzed, and 89% of these children are deceased. Similarly, LOH at 11q was detected in 32% of KWT, and 80% of these patients are deceased. From this genomic analysis, KWT biology appears uniquely aggressive and treatment-resistant., (© 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.)

MicroRNAs are important negative regulators of protein-coding gene expression and have been studied intensively over the past years. Several measurement platforms have been developed to determine relative miRNA abundance in biological samples using different technologies such as small RNA sequencing, reverse transcription-quantitative PCR (RT-qPCR) and (microarray) hybridization. In this study, we systematically compared 12 commercially available platforms for analysis of microRNA expression. We measured an identical set of 20 standardized positive and negative control samples, including human universal reference RNA, human brain RNA and titrations thereof, human serum samples and synthetic spikes from microRNA family members with varying homology. We developed robust quality metrics to objectively assess platform performance in terms of reproducibility, sensitivity, accuracy, specificity and concordance of differential expression. The results indicate that each method has its strengths and weaknesses, which help to guide informed selection of a quantitative microRNA gene expression platform for particular study goals.

Stearidonic acid (SDA), a highly unsaturated (n-3) PUFA, is effectively metabolized to EPA with a bioequivalence of ~5:1 as determined by the omega-3 index, a biomarker for risk of cardiovascular disease. The AHA has recommended that individuals increase their consumption of highly unsaturated (n-3) PUFA, particularly EPA and DHA, but there are concerns about achieving the recommendations through fish consumption. SDA is considered a biological surrogate for EPA. SDA-enriched soybean oil whose SDA content is ~30% could be a novel mechanism to seamlessly incorporate highly unsaturated (n-3) PUFA into the food supply; however, the effects of SDA are poorly understood, particularly at the transcriptional level. This paper reviews the human literature of the effects of dietary SDA on circulating lipids as directly compared with EPA at bioequivalent doses. These results were then compared to the effects of SDA on expression patterns of hepatic lipolytic and lipogenic genes in swine fed diets containing SDA at levels similar with those doses used in human trials. Supplementing SDA at doses of 3.7-4.2 g/d, of which the bioequivalence to EPA is ≤1 g/d, had little impact on modifying circulating TG and total, LDL, and HDL cholesterol, recapitulating the results with EPA at doses of 1.0-1.5 g/d. These results were generally supported by the gene expression patterns in swine. Although many lipolytic and lipogenic genes remained unchanged, several lipogenic genes were downregulated and a number of other biomarkers considered atheroprotective, such as C-reactive protein and paraoxonase, were favorably modified.

Background/aim: High-calcium diets modulate energy metabolism and suppress inflammatory stress. These effects are primarily mediated by calcium suppression of calcitriol. We have now investigated the effect of additional components in dairy products [branched-chain amino acids (BCAA) and angiotensin-converting enzyme inhibitors (ACEi)] on adipocyte and muscle metabolism in an animal model of diet-induced obesity., Methods: aP2-agouti mice were fed four different 70% restricted diets for 6 weeks: basal-restricted diet (0.4% Ca), nonfat dry milk (1.2% Ca), calcium-depleted milk (0.4% Ca), or basal-restricted diet (0.4% Ca) with supplemented BCAA/ACEi. A high-density oligonucleotide microarray approach was used to compare the effects on energy metabolism., Results: Lipogenic genes in adipose tissue were downregulated in the milk group while in muscle protein synthetic pathways were stimulated by the Ca-depleted and low Ca/BCAA/ACEi diets. Pathways involved in inflammation were altered in adipose tissue and muscle by all three diet treatment groups., Conclusions: The results support our previous findings that calcium and BCAA contribute to the alteration of energy partitioning between adipose tissue and muscle. They provide further evidence for a calcium-independent effect of BCAA and ACEi in energy metabolism and inflammation., (Copyright 2009 S. Karger AG, Basel.)

Nonalcoholic fatty liver disease (NAFLD), the major cause of global chronic hepatic injury, has obtained increasing attention while the current drug treatment still laid safety hazards. Major royal jelly proteins (MRJPs), the water-soluble proteins enriched in royal jelly (RJ), were applied to study its effects on improving NAFLD in the NAFLD mouse model. Herein, we demonstrated that intaking of 250-500 mg/kg/day MRJPs significantly decreased the rate of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. Next, TOF to MRM ("TM") widely targeted metabolomics (untargeted metabolomics + widely targeted metabolomics) was further used to explore the potential mechanism, and we found that 500 mg/kg MRJPs alleviated lipid metabolism, oxidative stress, and inflammation mainly by regulating the metabolisms of alpha-linolenic acid, linoleic acid, arachidonic acid, and biosynthesis of unsaturated fatty acids. Moreover, by detecting multiple oxidative stress factors and inflammatory cytokines, we found that MRJPs indeed exerted antioxidant and anti-inflammatory effects. Together, we demonstrated that MRJPs could mediate the progress of NAFLD through the "multi-component-multi-target-multi-pathway" mechanism, which could be considered as an ideal functional food in alleviating NAFLD. PRACTICAL APPLICATIONS: Royal jelly (RJ) is a bee product with high nutritional value. Major royal jelly proteins (MRJPs) are water-soluble proteins in RJ. Our research showed that MRJPs significantly ameliorated NAFLD induced by a high-fat diet in mice, suggesting that MRJPs could be used as an active ingredient to help improve NAFLD, which was beneficial for the development of related functional foods and the economic value of RJ. Moreover, the metabolic pathways involved in the ameliorative effect of MRJPs were investigated, which provided new ideas for the prevention and treatment of NAFLD., (© 2022 Wiley Periodicals LLC.)

Dinitrotoluene (DNT) has been extensively used in manufacturing munitions, polyurethane foams and other important chemical products. However, it is highly toxic and mutagenic to most organisms. Here, we synthesized a codon-optimized bacterial nitroreductase gene, NfsI, for plant expression. The kinetic analysis indicates that the recombinant NfsI can detoxify both 2,4-DNT and its sulfonate (DNTS), while it has a 97.6-fold higher catalytic efficiency for 2,4-DNT than DNTS. Furthermore, we overexpressed NfsI in switchgrass (Panicum virgatum L.), which is a multiple-purpose crop used for fodder and biofuel production as well as phytoremediation. The 2,4-DNT treatment inhibited root elongation of wild-type switchgrass plants and promoted reactive oxygen species (ROS) accumulation in roots. In contrast, overexpression of NfsI in switchgrass significantly alleviated 2,4-DNT-induced root growth inhibition and ROS overproduction. Thus, the NfsI overexpressing transgenic switchgrass plant removed 94.1% 2,4-DNT after 6 days, whose efficiency was 1.7-fold higher than control plants. Moreover, the comparative transcriptome analysis suggests that 22.9% of differentially expressed genes induced by 2,4-DNT may participate in NfsI-mediated 2,4-DNT detoxification in switchgrass. Our work sheds light on the function of NfsI during DNT phytoremediation for the first time, revealing the application potential of switchgrass plants engineered with NfsI., (© 2021 John Wiley & Sons Ltd.)

Down syndrome (DS) is one of the most common causes of intellectual disability and new approaches allowing its rapid and effective prenatal detection are being explored. In this study, we investigated the diagnostic potential of plasma microRNAs (miRNAs). This study builds upon our previous study in DS placentas, where seven miRNAs were found to be significantly up-regulated. A total of 70 first-trimester plasma samples from pregnant women were included in the present study (35 samples with DS fetuses; 35 with euploid fetuses). Genome-wide miRNA profiling was performed in the pilot study using Affymetrix GeneChip™ miRNA 4.1 Array Strips (18 samples). Selected miRNAs were then analysed in the validation study using quantitative reverse transcription PCR (RT-qPCR; 52 samples). Based on the current pilot study results (12 miRNAs), our previous research on chorionic villi samples (7 miRNAs) and the literature (4 miRNAs), a group of 23 miRNAs was selected for the validation study. Although the results of the pilot study were promising, the validation study using the more sensitive RT-qPCR technique and a larger group of samples revealed no significant differences in miRNA profiles between the compared groups. Our results suggest that testing of the first-trimester plasma miRNAs is probably not suitable for non-invasive prenatal testing (NIPT). Different results could be theoretically achieved at later gestational ages; however, such a result probably would have limited use in clinical practice.